1. Field of the Invention
The present invention relates to a device for monitoring the operation of a drug delivery system, in particular an insulin delivery system, a drug delivery system comprising the device and the method of use of the device.
2. Discussion of the Prior Art
Delivery systems including the device of the present invention are suitable for use not only for medical treatment purposes but also as batch feeders in analytical laboratories, the chemical and pharmaceutical industries and other technologies.
Insulin delivery systems usually provide infusions in two forms: (1) the basal flow rates aimed to cover the daily requirement of insulin of the body and (2) supplementary flow rates meant to compensate for meals. In some constructions, infusions can also be adjusted to account for increased physical activity or for increased demand caused by the "dawn phenomenon".
Insulin is infused in very small amounts on the order of some microliters per hour. For technical reasons, it is very difficult for pumps to deliver such small amounts as a constant flow. Instead, they can be controlled to perform a single pumping cycle delivering on the order of 1 .mu.l at intervals of several minutes. In connection with meals, pumps may be manually controlled to perform with high frequency a series of pumping cycles as bolus infusions.
Safe operation of a drug delivery system is a fundamental requirement as a malfunction of the system can cause either an overdose of the hormone or a lack of infusion of the hormone which constitute serious hazards to the life of a patient.
Furthermore, devices for monitoring the operation of a drug delivery system should be as compact as possible in order to be easily portable. Therefore, the number of measuring units such as sensors and monitors should be as few as possible.
A number of different constructional solutions of portable and implantable drug delivery systems exist.
Two examples of such systems are the Betatron I.TM. and II.TM. (manufactured by Cardiac Pacemakers Inc.). In these systems, the following alarm states are signal led: Supply voltage drop, an empty drug reservoir, blockage of the outlet catheter, microcomputer breakdown, the failure of the internal memory of the system, a too high frequency of the pump operation, a motor breakdown, a dose of insulin in excess of the established daily dose of insulin and erroneous initial data input (improper programming of the infusion). The Betatron I.TM. and II.TM. delivery systems are described in Health Devices, Nov. 1987, "Ambulatory Insulin Infusion Pumps", pp. 351-376 (in which nine ambulatory insulin infusion pumps are evaluated).
In another construction, MRS-1.TM. (manufactured by Disetronic AG/Ltd.), the following alarm states are detected: Electronic systems, the supply battery, the drug level in the reservoir, outlet catheter patency and the administration of an excess dose of insulin in the form of bolus infusions.
In the solutions mentioned above, alarm states such as an empty drug reservoir, a too high frequency of the operation of the pump or a dose of insulin in excess of the daily allowable insulin dose are determined by counting control impulses fed to the pump. Hence, these monitoring systems provide merely indirect monitoring of the correctness of an insulin infusion. This is also true of other alarm states. For instance, monitoring of the operation of the pump (flow control) is carried out by measuring the movement of its mechanical parts.
Clinical applications of insulin delivery systems have indicated that during long-term continuous insulin infusion (especially when implantable systems are used), one of the most frequent technical problems is connected with blockage of the outlet catheter. In order to solve this problem, monitoring of the threshold pressure in the outlet catheter has been used.
An exemplary solution of such monitoring with a view to "catheter plugging" was developed by Siemens and is described in K. Prestele and M. Frentzki, "State of Development of Program-Controlled Implantable Insulin Delivery Systems" in "Artificial Systems for Insulin Delivery" edited by P. Brunetti et al., 1983, Raven Press, New York, pp. 141-153. According to this system, the measurement of the pressure is performed as an indirect non-quantitative check of the flow of insulin through the pump outlet.
This system consists of a non-conducting cylinder having a diameter equal to the inner diameter of the catheter, two electrodes and a unit for measuring the conductivity in the circuit: Electrode--catheter section containing the cylinder--electrode. During normal operation of the pump, overpressure is generated which causes an increase in both the diameter of the catheter and the flow of the insulin (which is a conductor) around the cylinder. A blockage of the catheter results in a much stronger signal than the signal during normal operation. If the pressure threshold value is exceeded by 1 bar the alarm is switched on.
Other examples of technical solutions in which pressure monitoring has been utilized are described below.
U.S. Pat. No. 4,551,133, entitled "Patient Controlled Medication Infusion System" (by Zegers de Beyl), describes a system which is capable of monitoring the physiological conditions of the patient (respiratory and heart rates) by providing a pressure transducer which is in fluid wave pressure communication (placed directly or indirectly--sensor connected to a syringe plunger) with the fluid being infused into the peripheral vein of the patient through an infusion line. This system can also detect the infiltration or occlusion of the infusion line.
The microprocessor used in this system continuously tracks the amplitude of the signal and keeps the amplitude constant using an automatic gain control amplifier. Additionally, (when the pump is not operating) the static pressure is measured in the infusion line. The microprocessor is programmed to measure the amount of gain control which must be applied to the signal during normal operation of the pump and to measure the initial level of static pressure in the infusion line. The microprocessor monitors the physiological conditions of the patient (respiratory rate, heart rate), automatic gain control value and static pressure, by averaging these values over a preselected period of time, such as two minutes, and then comparing them with preselected reference limit values.
When the amount of gain goes beyond a certain threshold toward a maximum, the microprocessor recognizes that the signal has been lost. The loss of the signal indicates the infiltration and/or occlusion of the infusion line. This device can measure, based on two minute intervals, average respiratory and heart rates of the patient as well as check every two minutes whether the infusion line between the pump and the patient is occluded and/or infiltered.
However, the device cannot monitor the operation of a delivery system. This is underlined by the fact that according to Zegers an occlusion of the catheter means loss of signal. On the other hand, as shown below, the device for monitoring the operation of a delivery system according to the present invention will cause a powerful signal in the case of catheter blockage.
In European Patent Application No. 0,296,124, "Pump, Particularly for Enteral Fluid Control, Cassette for Pump, and Method of Operating Pump" (Frantz Medical Development Ltd.), a pressure transducer is used for monitoring three alarm states, (1) an empty cassette receiving chamber, (2) an upstream blockage or occlusion in the supply tube, and (3) a downstream blockage or occlusion such as the patient kinking output tube.
According to Frantz, alarm states are determined by a piezoelectric disc transducer placed between the piston and bellows chamber which detects the pressure inside the pump driving system, i.e., monitoring of the alarm states is determined outside the infusion line. During normal pumping, the piston and transducer remain in contact with the cassette bellows thus producing an electric signal which is comparable to the reference value. In the case of downstream occlusion, the peak of the pressure curve is higher than the peak of the normal voltage signal. This indicates that the piston is encountering more than usual resistance in compressing the bellows. In the case of upstream occlusion, the typical bell curve described by the pressure signal from the transducer is shifted some milliseconds later with respect to the motor cycle and piston movement. Finally, if a cassette is not properly latched into the cassette-receiving chamber, the transducer output signal remains at 0 volts due to the fact that there is no contact between the piston and bellows, and the transducer is not pressurized.
In the prior art systems mentioned above, alarm states are determined by many different methods. These monitoring systems provide merely indirect monitoring of the correctness of a drug infusion, i.e., the measurements concerning the relation between certain parts of the driving system are not directly connected with the state of fluid infusion, and consequently there is no guarantee that the drug is actually introduced into the body of the patient. For example, the prior art devices cannot be used for determining whether the pump is feeding air instead of the drug.
Furthermore, the prior art solutions are all examples of "open-loop" units for continuous monitoring of the operation of portable drug delivery systems, i.e., they cannot use the measurements to correct the operation of the pump.
It is the object of the present invention to provide a device which accurately monitors the operation of a drug delivery system and therefore guarantees that the drug is infused into the body of the patient.
It is also the object of the present invention to provide a device for monitoring the operation of a drug delivery system which is compact and easily portable, i.e., a device which can be used in small portable units to realize long-term continuous drug infusion. It is also the object of the present invention to provide a device which can operate as a closed-loop system.